Randomized Trial of Two Induction Therapy Regimens for High-Risk Neuroblastoma: HR-NBL1.5 International Society of Pediatric Oncology European Neuroblastoma Group Study

被引：50

作者：

Garaventa, Alberto ^{[1
]}

Poetschger, Ulrike ^{[2
]}

Valteau-Couanet, Dominique ^{[3
]}

Luksch, Roberto ^{[4
]}

Castel, Victoria ^{[5
]}

Elliott, Martin ^{[6
]}

Ash, Shifra ^{[7
]}

Chan, Godfrey C. F. ^{[8
,9
]}

Laureys, Genevieve ^{[10
]}

Beck-Popovic, Maja ^{[11
]}

Vettenranta, Kim ^{[12
]}

Balwierz, Walentyna ^{[13
]}

Schroeder, Henrik ^{[14
]}

Owens, Cormac ^{[15
]}

Cesen, Maja ^{[16
]}

Papadakis, Vassilios ^{[17
]}

Trahair, Toby ^{[18
]}

Schleiermacher, Gudrun ^{[19
]}

Ambros, Peter ^{[2
]}

Sorrentino, Stefania ^{[1
]}

Pearson, Andrew D. J. ^{[20
,21
]}

Ladenstein, Ruth Lydia ^{[22
,23
]}

机构：

[1] IRCCS Ist Giannina Gaslini, Genoa, Italy

[2] Childrens Canc Res Inst, Vienna, Austria

[3] Gustave Roussy, Paris, France

[4] Fdn IRCCS Ist Nazl Tumori, Milan, Italy

[5] Hosp Univ I Politecn La Fe, Pediat Oncol Unit, Valencia, Spain

[6] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England

[7] Ruth Rappaport Childrens Hosp, Rambam Hlth Care Campus, Haifa, Israel

[8] Univ Hong Kong, Hong Kong, Peoples R China

[9] Hong Kong Childrens Hosp, Hong Kong, Peoples R China

[10] Univ Hosp Ghent, Ghent, Belgium

[11] Univ Hosp Lausanne, Lausanne, Switzerland

[12] Univ Helsinki, Childrens Hosp, Helsinki, Finland

[13] Jagiellonian Univ Med Coll, Krakow, Poland

[14] Univ Hosp Aarhus, Dept Paediat, Aarhus, Denmark

[15] Univ Dublin, Dublin, Ireland

[16] Pediat Clin, Ljubljana, Slovenia

[17] Agia Sofia Childrens Hosp, Athens, Greece

[18] Sydney Childrens Hosp, Randwick, NSW, Australia

[19] Inst Curie, Paris, France

[20] Inst Canc Res, Sutton, Surrey, England

[21] Royal Marsden Hosp, Sutton, Surrey, England

[22] Med Univ, Dept Paediat, St Anna Childrens Hosp, Vienna, Austria

[23] Med Univ, Childrens Canc Res Inst, Vienna, Austria

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2021年 / 39卷 / 23期

关键词：

STAGE-4; NEUROBLASTOMA; OPEN-LABEL; CHILDREN OLDER; RAPID COJEC; CHEMOTHERAPY; AGE; DOXORUBICIN; TOPOTECAN; MELPHALAN; BUSULFAN;

D O I：

10.1200/JCO.20.03144

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]). PATIENTS AND METHODS Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged < 1 year with MYCN amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS. RESULTS A total of six hundred thirty patients were randomly assigned to receive rCOJEC (n = 313) or MSKCC-N5 (n = 317). Median age at diagnosis was 3.2 years (range, 1 month to 20 years), and 16 were younger than 1 year of age with MYCN amplification. mCR rate following rCOJEC induction (32%, 86/272 evaluable patients) was not significantly different from 35% (99/281) with MSKCC-N5 (P = .368), and 3-year EFS was 44% +/- 3% for rCOJEC compared with 47% +/- 3% for MSKCC-N5 (P = .527). Three-year overall survival was 60% +/- 3% for rCOJEC compared with 65% +/- 3% for MSKCC-N5 (P = .379). Toxic death rates with both regimens were 1%. However, nonhematologic CTC grade 3 and 4 toxicities were higher with MSKCC-N5: 68% (193/283) versus 48% (129/268) (P < .001); infection 35% versus 25% (P = .011); stomatitis 25% versus 3% (P < .001); nausea and vomiting 17% versus 7% (P < .001); and diarrhea 7% versus 3% (P = .011). CONCLUSION No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.

引用

页码：2552 / +

页数：18

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